Prostaglandins have been implicated to play a role in many aspects of renal function. Specifically, renal prostaglandin-E2 has been shown to be a potent modulator of sodium and water metabolism and of renal blood flow under experimental conditions. This proposal will attempt to better define the relatinship of renal prostaglandin release to changes in sodium excretion in normal and pathologic states. After defining the magnitude of prostaglandin release in a group of chronically instrumented conscious dogs, various maneuvers will be performed to attempt to modulate prostaglandin release by changing the magnitude of sodium excretion. Once these have been observed, various inhibitors of prostaglandin synthesis will be given to the same animals both acutely and chronically to attempt to influence the changes noted in sodium excretion. To study changes in prostaglandin release associated with sodium retaining states, the animals will be subjected to 1) acute and chronic salt loads, 2) large doses of mineralocorticoids, and 3) various surgical procedures to simulate edematous states (chronic A-V fistulae, thoracic vena cava obstruction, etc.). Changes in prostaglandin release associated with salt-wasting states will be studied with 1) diuretic agents, 2) partial ureteral obstruction, and 3) with surgically induced glucocorticoid deficiency. Recent literature has confirmed the association of prostaglandin release to diseases which are associated with changes in sodium excretion. This proposal will attempt to clarify the role of prostaglandin release in several well controlled models of alterations in sodium homeostasis. This knowledge should help to understand more of the basic mechanisms involved in the generation and maintenance of edematous states and in conditions associated with impaired ability to conserve sodium.